The production of nitric oxide in brain glial cells is stimulated by cytokines and requires the concomitant synthesis of tetrahydrobiopterin. Fibroblasts doubly transfected with tyrosine hydroxylase and GTP cyclohydrolase cDNAs spontaneously produce large amounts of dopamine and have been used in an animal model for Parkinson's disease. A new feedback regulatory protein (GFRP) which interacts with GTP cyclohydrolase has been cloned. The GFRP-GTP cyclohydrolase complex has low activity in the presence of tetrahydrobiopterin and the activity is specifically restored by L-phenylalanine, constituting a new type of metabolic regulation.